Can Treg Infusions Thwart the Immune Response in Type 1 Diabetes?

A lot of people, when they first get diabetes, think that there’s nothing they can really do about it, aside from managing it as best as they can. Mary Rooney thought the opposite.

“My diagnosis was a total shock, a huge shock,” says Rooney, 38, who was diagnosed with type 1 diabetes three years ago. “But I moved from shock to action pretty quickly.”

The action that Rooney took was to enroll in phase I of a clinical trial that tested the safety of a procedure aimed at slowing down, and perhaps even stopping the destruction of pancreatic beta calls in type 1 diabetics.

Type 1 diabetes is caused when the body’s immune system—for reasons that are not entirely clear—attacks and kills beta cells. Beta cells produce insulin and if their destruction is curbed it could lead to improved treatment, or even a cure, for the condition.

Mary Rooney

What researchers are investigating through Rooney’s trial is whether or not another component of the immune system called T regulatory cells, or Tregs, can thwart the aggressive immune response that destroys beta cells, according to Dr. Douglas Losordo, Chief Medical Officer for NeoStem, the company developing and testing the Treg treatment.

Tregs were once called suppressor T cells because they work to modulate the immune system and theoretically prevent it from over responding and destroying healthy cells.

“We are trying to restore the immune balance that occurs in a normal person, or a person without diabetes,” Dr. Losordo says about the goals of the treatment.

One criteria for subjects to enroll in the trial testing the treatment was that they must have been diagnosed with type 1 diabetes within two years of taking part. The reason for this is so those enrolled are still experiencing some pancreatic beta cell function, according to Dr. Adel Nada, Vice President of Immunotherapy at NeoStem.

“I made a conscious decision after I was diagnosed to stay positive,” Rooney says. “For me part of staying positive was to do something; to take action.”

While acknowledging that clinical trials carry risks and are never a medical treatment because they are purely experimental, Rooney says she turned to becoming a subject in a trial in part because she was familiar with them. As a clinical psychologist she had sat on the other side of the table and tested children in trials on the effectiveness of various interventions for treating Attention Deficit Hyperactivity Disorder, or ADHD.

Logistically, she specifically decided to enroll in the Treg trial for two reasons. The first was that it was being administered near her Bay area home at the University of California San Francisco. Her second reason was that if the trial had positive results it might extend her honeymoon period, or the time shortly after diagnosis when a person’s beta cells are still producing some insulin.

In a larger sense, though, Rooney’s decision to enroll in the trial was driven by a desire to contribute to helping research into a cure as well as helping herself to not feel powerless in the face of her condition.

“At first I thought, ‘Why me?’” Rooney says about her diagnosis. “Well, the flip side of that is, ‘Why not me?’ Once I thought about that I made a conscious decision to try and help myself stay positive. The trial was a big part of that.”

Rooney adds that she went into the trial knowing there were risks, such as possible side effects. She also says that in addition to potential known side effects, the trial—like all clinical trials—carried unknown, and unknowable, risks.

“You’re modifying your immune system,” she says. “Everything about doing that is not fully understood.”

The actual trial procedure was fairly straightforward.

According to Dr. Nada, researchers drew Rooney’s blood and separated out the Tregs. Once separated Rooney’s Treg cells were then “sort of bombarded with antibodies,” Nada says. “After new cells are generated they are then packaged, if you will, and infused back into the subject. It’s a simple procedure.”

Rooney says the actual procedure took all of 15 minutes. However, she did have to spend the next 24 hours in the hospital under observation; a time, Rooney says, that was “really boring.”

The results of the first phase of the trial have so far been positive for Rooney, and for the researchers.

“I’m still producing my own insulin,” says Rooney, who continues to go for periodic follow-up visits. “I basically had no side effects from the infusion and continue to have no side effects.”

In June NeoStem announced that the trial overall was successful.

“Treg infusions were safe and well tolerated and the majority of [adverse effects] were mild, indicating a favorable safety profile for a single infusion of Tregs,” according to a report from LifeSci Advisors Research, an investor relations firm. “Average stimulated C-peptide levels [a measurement of insulin in the body] remained stable for as long as 2 years following treatment, suggesting that a single infusion may have long lasting effects.”

Phase II of the trial is expected to start in the third quarter of this year, the report concluded.

Meanwhile, Rooney is not sitting around thinking she is cured.

“If I thought of this as a treatment even, then I might slack off on taking care of myself,” says Rooney, who wears an insulin pump and sticks to a moderate carb diet and exercises regularly. “What I went through is experimental and is not a treatment. I have no expectation of what might happen in the future with me. Right now I’m just happy that I was able to do something about my diabetes rather than just sitting around.”